Abstract
BackgroundMesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al. recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). The purpose of this study was to quantify the expression of ACE2 and TMPRSS2 in hUC-MSCs lots derived from multiple donors using molecular-based techniques in order to demonstrate their inability to be a host to SARS-CoV-2.MethodsExpression of ACE2 and TMPRSS2 was analyzed in 24 lots of hUC-MSCs derived from Wharton's jelly via quantitative polymerase chain reaction (qPCR), Western Blot, immunofluorescence and flow cytometry using 24 different donors.ResultshUC-MSCs had significantly lower ACE2 (p = 0.002) and TMPRSS2 (p = 0.008) expression compared with human lung tissue homogenates in Western blot analyses. Little to no expression of ACE2 was observed in hUC-MSC by qPCR, and they were not observable with immunofluorescence in hUC-MSCs cell membranes. A negative ACE2 and TMPRSS2 population percentage of 95.3% ± 15.55 was obtained for hUC-MSCs via flow cytometry, with only 4.6% ACE2 and 29.5% TMPRSS2 observable positive populations.ConclusionsWe have demonstrated negative expression of ACE2 and low expression of TMPRSS2 in 24 lots of hUC-MSCs. This has crucial implications for the design of future therapeutic options for COVID-19, since hUC-MSCs would have the ability to “dodge” viral infection to exert their immunomodulatory effects.
Highlights
Mesenchymal stem cells derived from human umbilical cord have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19)
We investigated the expression of Angiotensin-Converting Enzyme 2 (ACE2) and TMPRSS2 in hUC-Mesenchymal stem cells (MSCs) lines derived from different donors using quantitative polymerase chain reaction, Western Blot, immunofluorescence and flow cytometry
TMPRSS2 levels were variable between hUC-MSCs from different donors
Summary
Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). Mesenchymal stem cells (MSCs) [12, 13] exert antiinflammatory [14,15,16], anti-bacterial, anti-protozoan and anti-viral [17,18,19,20] effects making them a possible treatment for COVID-19-related complications [21,22,23,24]. In a study of 150 people with confirmed cases of COVID-19, levels of the inflammatory cytokine IL-6 were significantly higher in non-survivors than in survivors of the disease [29]. UC-MSCs have been used to modulate IL-6 in the body: for example, the levels of IL-6 decreased around 50% three months after treatment in a study of 172 patients with rheumatoid arthritis [31]
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